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WO1998011229A3 - Histidine-tagged shiga toxins, toxoids, and protein fusions with such toxins and toxoids, methods for the purification and preparation thereof - Google Patents

Histidine-tagged shiga toxins, toxoids, and protein fusions with such toxins and toxoids, methods for the purification and preparation thereof Download PDF

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Publication number
WO1998011229A3
WO1998011229A3 PCT/US1997/015836 US9715836W WO9811229A3 WO 1998011229 A3 WO1998011229 A3 WO 1998011229A3 US 9715836 W US9715836 W US 9715836W WO 9811229 A3 WO9811229 A3 WO 9811229A3
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WO
WIPO (PCT)
Prior art keywords
toxoids
toxins
purification
shiga
tagged
Prior art date
Application number
PCT/US1997/015836
Other languages
French (fr)
Other versions
WO1998011229A2 (en
Inventor
Alison D O'brien
Clare K Schmitt
Original Assignee
Jackson H M Found Military Med
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Jackson H M Found Military Med filed Critical Jackson H M Found Military Med
Priority to JP10513748A priority Critical patent/JP2001500730A/en
Priority to EP97939845A priority patent/EP0929679A2/en
Priority to AU41845/97A priority patent/AU4184597A/en
Priority to CA002265887A priority patent/CA2265887A1/en
Publication of WO1998011229A2 publication Critical patent/WO1998011229A2/en
Publication of WO1998011229A3 publication Critical patent/WO1998011229A3/en

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/195Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
    • C07K14/24Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Enterobacteriaceae (F), e.g. Citrobacter, Serratia, Proteus, Providencia, Morganella, Yersinia
    • C07K14/245Escherichia (G)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04Antibacterial agents
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/195Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
    • C07K14/24Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Enterobacteriaceae (F), e.g. Citrobacter, Serratia, Proteus, Providencia, Morganella, Yersinia
    • C07K14/25Shigella (G)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/51Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2319/00Fusion polypeptide

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Veterinary Medicine (AREA)
  • Communicable Diseases (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oncology (AREA)
  • Public Health (AREA)
  • General Chemical & Material Sciences (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)

Abstract

The present invention describes the isolation and purification of biologically and immunologically active histidine-tagged Shiga toxins (His-tagged), a toxin associated with HC and the potentially life-threatening sequela HUS transmitted by strains of pathogenic bacteria. The present invention describes how his-tagging greatly simplifies and expedites purifying Shiga toxins, and describes an improved method for such purification. One aspect of the invention is obtaining and using Shiga toxoids that are immunoreactive but not toxic. Another aspect of the invention is obtaining and using fusion proteins of His-tagged Shiga toxins or toxoids. Yet another aspect of the invention is obtaining and using antibodies to His-gagged Shiga toxins, toxoids, or Shiga toxin/toxoid fusion proteins.
PCT/US1997/015836 1996-09-10 1997-09-09 Histidine-tagged shiga toxins, toxoids, and protein fusions with such toxins and toxoids, methods for the purification and preparation thereof WO1998011229A2 (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
JP10513748A JP2001500730A (en) 1996-09-10 1997-09-09 Histidine-tagged Shiga toxin and toxoid, fusion protein with the toxin and toxoid, and methods for purification and preparation thereof
EP97939845A EP0929679A2 (en) 1996-09-10 1997-09-09 Histidine-tagged shiga toxins, toxoids, and protein fusions with such toxins and toxoids, methods for the purification and preparation thereof
AU41845/97A AU4184597A (en) 1996-09-10 1997-09-09 Histidine-tagged shiga toxins, toxoids, and protein fusions with such toxins and toxoids, methods for the purification and preparation thereof
CA002265887A CA2265887A1 (en) 1996-09-10 1997-09-09 Histidine-tagged shiga toxins, toxoids, and protein fusions with such toxins and toxoids, methods for the purification and preparation thereof

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US2563796P 1996-09-10 1996-09-10
US60/025,637 1996-09-10

Publications (2)

Publication Number Publication Date
WO1998011229A2 WO1998011229A2 (en) 1998-03-19
WO1998011229A3 true WO1998011229A3 (en) 1998-04-16

Family

ID=21827219

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1997/015836 WO1998011229A2 (en) 1996-09-10 1997-09-09 Histidine-tagged shiga toxins, toxoids, and protein fusions with such toxins and toxoids, methods for the purification and preparation thereof

Country Status (6)

Country Link
EP (1) EP0929679A2 (en)
JP (1) JP2001500730A (en)
AR (1) AR010218A1 (en)
AU (1) AU4184597A (en)
CA (1) CA2265887A1 (en)
WO (1) WO1998011229A2 (en)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7157418B1 (en) 1998-07-22 2007-01-02 Osprey Pharmaceuticals, Ltd. Methods and compositions for treating secondary tissue damage and other inflammatory conditions and disorders
US10815469B2 (en) 2014-06-11 2020-10-27 Molecular Templates, Inc. Cell-targeting molecules comprising protease-cleavage resistant, Shiga toxin A subunit effector polypeptides and carboxy-terminal moieties
US11104707B2 (en) 2015-02-05 2021-08-31 Molecular Templates, Inc. Multivalent CD20-binding molecules comprising Shiga toxin a subunit effector regions and enriched compositions thereof
US11225509B2 (en) 2018-04-17 2022-01-18 Molecular Templates, Inc. HER2-targeting molecules comprising de-immunized, Shiga toxin A subunit scaffolds
US11312751B2 (en) 2014-01-27 2022-04-26 Molecular Templates, Inc. MHC class I epitope delivering polypeptides
US11365223B2 (en) 2015-05-30 2022-06-21 Molecular Templates, Inc. De-immunized, Shiga toxin a subunit scaffolds and cell-targeting molecules comprising the same
US11389542B1 (en) 2016-12-07 2022-07-19 Molecular Templates, Inc. Shiga toxin a subunit effector polypeptides, Shiga toxin effector scaffolds, and cell-targeting molecules for site-specific conjugation
US11406692B2 (en) 2017-01-25 2022-08-09 Molecular Templates, Inc. Cell-targeting molecules comprising de-immunized, Shiga toxin a subunit effectors and CD8+ t-cell epitopes

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2766193B1 (en) 1997-07-18 2001-09-14 Inst Curie CHEMICAL POLYPEPTIDE COMPRISING FRAGMENT B OF TOXIN SHIGA AND PEPTIDES OF THERAPEUTIC INTEREST
GB9715177D0 (en) * 1997-07-21 1997-09-24 Neutec Pharma Plc Medicament
US20020081307A1 (en) * 1998-05-15 2002-06-27 Allan M. Green Verotoxin b subunit for immunization
EP1057895A1 (en) * 1999-06-04 2000-12-06 Lohmann Animal Health GmbH & Co. KG Fusion protein comprising Shiga toxin 2e B subunit, (vaccine)compositions comprising it, and methods for their production
WO2007098201A2 (en) * 2006-02-16 2007-08-30 The Henry M. Jackson Foundation For The Advancement Of Military Medicine, Inc. Shiga toxoid chimeric proteins
JP2009536818A (en) * 2006-04-20 2009-10-22 ザ ヘンリー エム. ジャクソン ファウンデーション フォー ザ アドヴァンスメント オブ ミリタリー メディシン インコーポレイテッド Methods and compositions based on Shiga toxic type 1 protein
US8969529B2 (en) 2009-01-23 2015-03-03 The Henry M. Jackson Foundation For The Advancement Of Military Medicine, Inc. Methods and compositions based on shiga toxin type 2 protein
KR101990341B1 (en) * 2013-03-12 2019-06-19 몰레큘러 템플레이츠, 인코퍼레이션. Cd20-binding immunotoxins for inducing cellular internalization and methods using same
US11142584B2 (en) 2014-03-11 2021-10-12 Molecular Templates, Inc. CD20-binding proteins comprising Shiga toxin A subunit effector regions for inducing cellular internalization and methods using same
EP3604333B1 (en) * 2014-03-11 2021-05-05 Molecular Templates, Inc. Proteins comprising amino-terminal proximal shiga toxin a subunit effector regions and cell-targeting immunoglobulin-type binding regions capable of specifically binding cd38
EP3825327A1 (en) * 2014-03-11 2021-05-26 Molecular Templates, Inc. Proteins comprising binding regions, shiga toxin a subunit effector regions, and carboxy-terminal, endoplasmic reticulum localization signal motifs

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996012802A1 (en) * 1989-10-31 1996-05-02 Ophidian Pharmaceuticals, Inc. Vaccine and antitoxin for treatment and prevention of c. difficile disease
WO1996030043A1 (en) * 1995-03-24 1996-10-03 Ophidian Pharmaceuticals Treatment for verotoxin-producing escherichia coli

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996012802A1 (en) * 1989-10-31 1996-05-02 Ophidian Pharmaceuticals, Inc. Vaccine and antitoxin for treatment and prevention of c. difficile disease
WO1996030043A1 (en) * 1995-03-24 1996-10-03 Ophidian Pharmaceuticals Treatment for verotoxin-producing escherichia coli

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
FRYXELL D. ET AL.: "Genetic construction of a phosphorylation site in ricin A chain: Specific radiolabeling of recombinant proteins for localization and degradation studies.", BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, vol. 210, no. 2, 1995, pages 253 - 259, XP002054492 *
GORDON V.M. ET AL.: "An enzymatic mutant of Shiga-like toxin II variant is a vaccine candidate for Edema disease of swine.", INFECTION AND IMMUNITY, vol. 60, no. 2, 1992, pages 485 - 490, XP002054488 *
HOCHULI E. ET AL.: "Genetic approach to facilitate purification of recombinant proteins with a novel metal chelate adsorbent.", BIOTECHNOLOGY, vol. 6, no. 11, 1988, pages 1321 - 1325, XP002054489 *
LI J.: "Bacterial toxins.", CURRENT OPINION IN STRUCTURAL BIOLOGY, vol. 2, no. 4, 1992, pages 545 - 556, XP000335477 *
LINDGREN S. W. ET AL.: "The specific activities of Shiga-like toxin type II (SLT-II) and SLT-II-related toxin of Enterohemorrhagic Escherichia coli differ when measured by Vero cell cytotoxicity but not by mouse lethality.", INFECTION AND IMMUNITY, vol. 62, no. 2, 1994, pages 623 - 631, XP002054490 *
TANG D. ET AL.: "Genetic immunization is a simple method for eliciting an immune response.", NATURE, vol. 356, 1992, pages 152 - 154, XP000310569 *

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7166702B1 (en) 1998-07-22 2007-01-23 Osprey Pharmaceuticals, Ltd. Cytotoxic conjugates comprising a chemokine receptor targeting agent
US7192736B2 (en) 1998-07-22 2007-03-20 Osprey Pharmaceuticals, Ltd. Nucleic acid molecules encoding cytotoxic conjugates that contain a chemokine receptor targeting agent
US7157418B1 (en) 1998-07-22 2007-01-02 Osprey Pharmaceuticals, Ltd. Methods and compositions for treating secondary tissue damage and other inflammatory conditions and disorders
US11312751B2 (en) 2014-01-27 2022-04-26 Molecular Templates, Inc. MHC class I epitope delivering polypeptides
US12065469B2 (en) 2014-01-27 2024-08-20 Molecular Templates, Inc. De-immunized Shiga toxin a subunit effector polypeptides for applications in mammals
US12037367B2 (en) 2014-01-27 2024-07-16 Molecular Templates, Inc. MHC class I epitope delivering polypeptides
US10815469B2 (en) 2014-06-11 2020-10-27 Molecular Templates, Inc. Cell-targeting molecules comprising protease-cleavage resistant, Shiga toxin A subunit effector polypeptides and carboxy-terminal moieties
US11104707B2 (en) 2015-02-05 2021-08-31 Molecular Templates, Inc. Multivalent CD20-binding molecules comprising Shiga toxin a subunit effector regions and enriched compositions thereof
US11365223B2 (en) 2015-05-30 2022-06-21 Molecular Templates, Inc. De-immunized, Shiga toxin a subunit scaffolds and cell-targeting molecules comprising the same
US11389542B1 (en) 2016-12-07 2022-07-19 Molecular Templates, Inc. Shiga toxin a subunit effector polypeptides, Shiga toxin effector scaffolds, and cell-targeting molecules for site-specific conjugation
US11857628B2 (en) 2016-12-07 2024-01-02 Molecular Templates, Inc. Shiga toxin A subunit effector polypeptides, Shiga toxin effector scaffolds, and cell-targeting molecules for site-specific conjugation
US11406692B2 (en) 2017-01-25 2022-08-09 Molecular Templates, Inc. Cell-targeting molecules comprising de-immunized, Shiga toxin a subunit effectors and CD8+ t-cell epitopes
US11225509B2 (en) 2018-04-17 2022-01-18 Molecular Templates, Inc. HER2-targeting molecules comprising de-immunized, Shiga toxin A subunit scaffolds

Also Published As

Publication number Publication date
WO1998011229A2 (en) 1998-03-19
CA2265887A1 (en) 1998-03-19
AR010218A1 (en) 2000-06-07
JP2001500730A (en) 2001-01-23
AU4184597A (en) 1998-04-02
EP0929679A2 (en) 1999-07-21

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